Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT01089101
• Date of registration: 17/03/2010
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
• Scientific title: A Phase 1 and Phase II and Re-Treatment Study of AZD6244 for Recurrent or Refractory Pediatric Low Grade Glioma
• Date of first enrolment: April 19, 2010
• Target sample size: 220
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01089101
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Jason R Fangusaro
• Affiliation: Pediatric Brain Tumor Consortium

Key inclusion & exclusion criteria

Inclusion Criteria:

- Imaging evaluations necessary to establish eligibility for study entry must be done
within three (3) weeks prior to registration

- All other evaluations necessary to establish eligibility for study entry must be done
within two (2) weeks prior to registration

- Patients must start therapy within 7 calendar days of registration

- Laboratory values must be no older than seven (7) days prior to the start of therapy;
if a test that is repeated after registration and prior to therapy is outside the
limits for eligibility, it must be rechecked within 48 hours prior to the start of
therapy; if laboratory values still fail to meet eligibility criteria, the patient may
not receive protocol therapy

- All patients must meet the following inclusion and exclusion criteria; NO EXCEPTIONS
WILL BE GIVEN

- Participant is willing to sign a screening consent and provide adequate pre-trial
tumor material for BRAF testing (both for BRAF V^600E mutation and BRAF KIAA1549
fusion assessments)

- All patients who are candidates for enrollment in stratum 5 based on their tumor
histology must be pre-screened

- Screening may be applied to potential stratum 1 and 2 patients

- Patients whose prior BRAF testing was performed at another lab (Clinical Laboratory
Improvement Amendments [CLIA]/College of American Pathologist [CAP] certified or
otherwise) must send additional tumor material to Brigham and Women's Hospital (BWH)
for confirmation; however, to preserve available tumor material, patients whose tumor
material has previously undergone BRAF analysis at the Lindeman and Ligon Labs at
Brigham and Women's Hospital using the same procedures as described in this protocol,
will not be required to submit additional tumor material for analysis; these patients
must have both the BRAFV600E mutation and BRAF KIAA1549 fusion assessments done and if
only one test was previously conducted; additional tissue will be required for the
second test

- Patient must be >= 3 but =< 21 years of age at registration

- Patient must have one of the following:

- For stratum 5: non NF-1 associated low grade glioma (LGG) (other than pilocytic
astrocytoma or optic pathway glioma)

- For stratum 1 or 2: non NF-1, non-optic pathway pilocytic astrocytoma; note: all
patients with non NF-1 associated optic pathway glioma with or without tissue
must be enrolled on stratum 4

- Patients with sporadic (non NF-1 associated), histologically diagnosed progressive,
recurrent or refractory non-optic pathway pilocytic astrocytoma who have pre-
treatment tumor tissue available for BRAF analysis

- NF-1 patients with radiographic evidence of a progressive, recurrent or refractory low
grade glioma, with or without pre-treatment tumor tissue

- Patients with progressive, recurrent or refractory optic pathway glioma, with or
without pre-treatment tumor tissue

- Patients with histologically diagnosed progressive, recurrent or refractory non NF-1
associated LGG (other than pilocytic astrocytoma or optic pathway glioma); these
patients must have BRAF aberrations as documented by the Lindeman and Ligon Labs at
Brigham and Women's Hospital using the same procedures

- Patients will be assigned to one of 6 strata prior to enrollment; all BRAF assessments
used for stratification below must be done at the Lindeman and Ligon Labs at Brigham
and Women's Hospital using the same procedures as described in this protocol;
assessments for both BRAF V^600E mutation and BRAF KIAA1549 fusion are required for
patients who will enroll on strata 1, 2 and 5

- Stratum 1: patients with non NF-1 associated progressive, recurrent or refractory
pilocytic astrocytoma with pre-trial tumor material available and with a BRAF
aberration i.e. BRAFV^600E mutation and/or BRAF KIAA1549 fusion as determined by
IHC and FISH, respectively; patients with optic pathway glioma are excluded

- Stratum 2: patients with non NF-1 associated progressive, recurrent or refractory
pilocytic astrocytoma with pre-trial tumor material available and without a BRAF
aberration i.e. BRAF^V600E mutation and/or BRAF KIAA1549 fusion as determined by
IHC and FISH, respectively; patients with optic pathway glioma are excluded

- Stratum 3: patients with neuro-fibromatosis 1 (NF-1) associated progressive,
recurrent or refractory low grade glioma (World Health Organization [WHO] grade I
& II), with or without tissue

- Stratum 4*: patients with non-NF1 associated progressive, recurrent or refractory
optic pathway glioma with or without tissue available for BRAF evaluation

- Stratum 5: patients with non NF-1 associated progressive, recurrent or refractory
low grade glioma other than pilocytic astrocytoma or optic pathway glioma with a
documented BRAF aberration identified in pre-trial tumor material

- Stratum 6: patients with non-NF-1 associated progressive, recurrent or refractory
low grade glioma (other than optic pathway glioma [OPG]) with tissue available
for BRAF analyses who cannot be classified into stratum 1, 2 or 5 due to
inadequate tissue quality, assay failure, etc

- Clarification: Stratum 4 was specifically designed for patients with
hypothalamic/optic pathway gliomas; the intent is that if there is any optic
chiasm invasion regardless of where the tumor is originating from (chiasm
vs. hypothalamus vs. other location), the patient should be enrolled on
Stratum 4, regardless of whether the tumor has been biopsied or not;
obviously, there are some tumors that include part of the hypothalamus and
clearly do NOT include the chiasm at all; in these situations, and if the
tumor is a biopsy proven pilocytic astrocytoma, these patients should be
enrolled on Stratum 1 or 2 (depending upon BRAF status)

- Patients must have bi-dimensionally measurable disease defined as at least one lesion
that can be accurately measured in at least two planes in order to be eligible for
this study

- Patients must have received prior therapy other than surgery and must have fully
recovered from the acute toxic effects of all prior chemotherapy, immunotherapy,
biologic therapy or radiotherapy prior to study entry

- Patients must have received their last dose of known myelosuppressive anticancer
chemother


Age minimum: 3 Years
Age maximum: 21 Years
Gender: All

Health Condition(s) or Problem(s) studied

Refractory Visual Pathway Glioma

Low Grade Glioma

Recurrent Neurofibromatosis Type 1

Recurrent Visual Pathway Glioma

Refractory Neurofibromatosis Type 1

Recurrent Childhood Pilocytic Astrocytoma

Intervention(s)

Procedure: Biospecimen Collection

Drug: Selumetinib

Primary Outcome(s)

Maximum tolerated dose and recommended phase 2 dose of selumetinib determined by dose-limiting toxicities (phase I) [Time Frame: 28 days]

Objective response (objective response = complete response + partial response) (re-treatment study) [Time Frame: Up to 48 weeks]

Disease stabilization rates (re-treatment study) [Time Frame: At 1 year]

Stratum-specific objective response (complete response + partial response) rate sustained for 8 weeks (phase II) [Time Frame: 40 weeks]

Secondary Outcome(s)

Plasma drug concentrations and pharmacokinetic parameters (Phase I) [Time Frame: Day 1 of cycle 1]

Stratum-specific progression-free survival distribution (PFS) (phase II) [Time Frame: From the date of initial treatment to the earliest date of disease progression, second malignancy or death for subjects who fail; and to the date of last contact for subjects who remain at risk for failure assessed for up to 30 days]

Presence or absence of BRAF V600E mutations or BRAF KIAA1549 fusion (phase II) [Time Frame: Up to 30 days]

Progression-free survival (retreatment study) [Time Frame: From the date of re-treatment initiation to the earliest date of disease progression, second malignancy or death for patients who fail; and the last contact for patients who remain at risk for failure, assessed up to 30 days]

Secondary ID(s)

CDR667932

U01CA081457

NCI-2012-03173

PBTC-029

PBTC-029B

UM1CA081457

Source(s) of Monetary Support

Please refer to primary and secondary sponsors